Prediction of response to neoadjuvant chemotherapy in breast cancer patients by circulating apoptotic biomarkers nucleosomes, DNAse, cytokeratin-18 fragments and survivin.

Biomarkers predicting response to neoadjuvant chemotherapy in locally confined breast cancer (LBC) are highly needed. We prospectively assessed serial blood levels of apoptotic biomarkers nucleosomes, DNAse activity, cytokeratin-18 fragments (M30) and survivin in 51 LBC patients and correlated them with response to neoadjuvant treatment and established tumor markers. As controls, we used 31 healthy subjects, 13 patients with benign diseases and 28 with metastatic breast cancer (MBC). Levels of nucleosomes and survivin were elevated in LBC and MBC while M30, CEA and CA 15-3 levels were only elevated in MBC. During neoadjuvant chemotherapy, LBC patients with no change of disease (N=13) had significantly higher pretherapeutic levels of nucleosomes than patients with remission (N=38). We conclude that apoptotic biomarkers bear valuable information for diagnosis and therapy response prediction in LBC patients.

Circulating immunogenic cell death biomarkers HMGB1 and RAGE in breast cancer patients during neoadjuvant chemotherapy.

Neoadjuvant chemotherapy in breast cancer patients aims at preoperative reduction of tumor volume for better resection results and prognosis. As not all patients respond to neoadjuvant therapy, predictive biomarkers are needed for more efficient individual management. In prospectively collected sera of 51 consecutive locally confined breast cancer (LBC) patients receiving preoperative, neoadjuvant chemotherapy, value level kinetics of soluble high mobility group box 1 (HMGB1), soluble receptor for advanced glycation end products (sRAGE) as well as the established breast cancer biomarkers CA 15-3 and carcinoembryonic antigen (CEA) were investigated and correlated with therapy response objectified by pathological staging at surgery. In addition, biomarkers were measured in sera of 30 healthy controls (HC), 13 patients with benign breast diseases, and 28 metastatic breast cancer (MBC) patients. Pretherapeutic levels of soluble HMGB1 were decreased in MBC, while sRAGE was already decreased in LBC. In contrast, CA 15-3 and CEA were strongly elevated in MBC, but not in LBC. Combination of sRAGE and CA 15-3 enabled best discrimination of LBC from HC (AUC 78.2 %; sens 58 % at 95 % spec), while CA15-3 and CEA discriminated best between MBC and all controls (AUC 90.9 %; sens 70 % at 95 % spec). In LBC patients undergoing neoadjuvant chemotherapy, nine patients achieved complete remission (CR), 29 achieved partial remission (PR), while 13 had no change of disease (NC). NC patients tended to have higher HMGB1 and lower sRAGE levels before therapy onset (p = 0.056 and p = 0.054), while CA 15-3 and CEA did not predict therapeutic outcome. Furthermore, kinetics of HMGB1 during therapy correlated with efficacy of the treatment (p = 0.053). Markers of immunogenic cell death are valuable for the diagnosis of MBC and early estimation of response to neoadjuvant therapy in LBC patients.

Duplex ultrasound imaging in free transverse rectus abdominis muscle, deep inferior epigastric artery perforator, and superior gluteal artery perforator flaps: early and long-term comparison of perfusion changes in free flaps following breast reconstruction.

OBJECTIVE: Our objective was to assess the hemodynamic differences in free DIEP (deep inferior epigastric artery perforator flap), S-GAP (superior gluteal artery perforator flap) flaps versus TRAM (transverse rectus abdominis muscle) flaps and to analyze any perfusion change due to perforator dissection (study 1). To examine the hypothesis as to whether flap perfusion is maintained through the pedicle (study 2), we also compared short- and long-term DIEP flap perfusion. MATERIAL AND METHODS: Blood volume flow, velocity, and diameter of the donor and recipient vessels of 4 TRAM flaps, 5 S-GAP flaps, and 17 DIEP flaps were examined preoperatively on day 5 and also 18 months postoperatively using duplex ultrasound. RESULTS: The greatest volume flow and velocity are measured in the TRAM flaps, followed by S-GAP and DIEP flaps. Blood flow in the musculocutaneous and perforator flaps is twice as great as in the donor vessels, which is proof of flap hyperperfusion. SUMMARY: The minimum perfusion requirement is easily satisfied in musculocutaneus and free perforator flaps. In the long term, DIEP flap perfusion increases 13%, which assumes that DIEP flap perfusion is maintained on the pedicle.

The "Gent" consensus on perforator flap terminology: preliminary definitions.

Due to its increasing popularity, more and more articles on the use of perforator flaps have been reported in the literature during the past few years. Because the area of perforator flaps is new and rapidly evolving, there are no definitions and standard rules on terminology and nomenclature, which creates confusion when surgeons try to communicate and compare surgical techniques. This article attempts to represent the opinion of a group of pioneers in the field of perforator flap surgery. This consensus was reached after a terminology consensus meeting held during the Fifth International Course on Perforator Flaps in Gent, Belgium, on September 29, 2001. It stipulates not only the definitions of perforator vessels and perforator flaps but also the correct nomenclature for different perforator flaps. The authors believe that this consensus is a foundation that will stimulate further discussion and encourage further refinements in the future.